Combining smoking information and molecular markers improves prognostication in patients with urothelial carcinoma of the bladder

Objectives: Tissue-based markers improve the accuracy of prediction models in urothelial carcinoma of the bladder (UCB). Current smoking status and cumulative exposure also affect outcomes. To evaluate whether the combination of molecular markers and smoking features further improved the prognostication of patients who underwent radical cystectomy (RC) for UCB. Materials and methods: A total of 588 patients underwent RC and bilateral lymphadenectomy for UCB from 1995 to 2005. Immunohistochemistry for p53, p21, pRB, p27, Ki-67, and survivin was performed on tissue microarrays from the RC specimen. Smoking features were routinely assessed at diagnosis. Multivariable Cox regression models assessed time to disease recurrence and cancer-specific mortality. Results: Of the 588 patients, 128 were never (22%), 283 former (48%), and 177 current smokers (30%). In total, 227 patients experienced disease recurrence, whereas 190 died of UCB. Smoking status was independently associated with both outcomes (hazard ratio [HR] = 1.48 and 2.62, for former and current vs. never smokers, respectively, P<0.001). All markers were significantly associated with both outcomes (P<0.05) except for survivin. The combination of the 4 cell cycle markers p53, p21, pRB, and p27 increased the discrimination of clinicopathologic model for former and current vs. never smokers with c-indices 0.779 and 0.780, respectively (base model c-indices of 0.741 and 0.740 for former and current vs. never smokers, respectively). The further addition of smoking features and biomarker status improved the discrimination of the model (c-indices of 0.783 and 0.786 for former and current vs. never smokers, respectively). Conclusions: We confirmed that smoking information and tissue markers status improve prognostication of UCB outcomes after RC; the combination of both reaching the highest level of discrimination.